From legal highs to legal supplies?

“Within five minutes I was tripping my balls off, trying to call friends for help, but I couldn’t use my phone. My heart rate was going up and I started to panic. …. I found myself in the street. The first thing I remember is being grabbed by a police officer and not knowing why. … The ambulance arrived and my heart rate was over 240 bpm”. (Guardian 27th April)

This is a seasoned user of legal and illegal drugs describing his experience of taking the relatively new psychedelic drug 25I-NBOMe. He was hospitalised for two days observation but survived.

The drug had already attracted the attention of the Advisory Committee on Drug Abuse (ACMD) and on May 16th, the Chair, Les Iversen, issued a warning about the serious risk of overdose associated with this new generation of psychedelic drugs. By May 29th, Iversen had recommended to the Home Secretary that the drugs should be banned temporarily. His recommendation was accepted and on June 10th, 25I-NBOMe and three similar drugs were banned for a year pending further investigation.

These events highlight both the problems currently facing the drug authorities and the risks facing users of these drugs. Until June 10th, it was perfectly legal to supply and use 25I-NBOMe and its analogues. They were “legal highs”, synthesised in labs in the Far East and supplied via UK web sites e.g. Lizard labs, Royal Alchemist. The risks to users were illustrated by a rash of hospitalisations in the North East associated with use of the drug. Seven cases of non-fatal intoxication were reported in January with one person suffering renal damage. Many of these cases had snorted the drug. There have also been reports of deaths following use of the drug in the USA
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I knew quite a bit about the archetypal psychedelic, LSD, but I hadn’t heard of the NBOMe series of drugs before. In fact very little is known about these compounds as I discovered when I had a look in PubMed and other data bases. If so little is known, then why have these compounds been dignified by a ban?

The drugs were first synthesised by Ralf Heim in Berlin in 2003 and three years later, David Nichols at Purdue made further analogues and characterised them. Structurally, the compounds are related to the naturally occurring psychedelic, mescaline but have additional chemical substituents that massively increase their potency. There are no controlled studies on the effects of these drugs in humans, but based on reports from recreational users, 25I-NBOMe is a psychedelic with effects similar but not identical to LSD. Users have also reported serious negative side effects.

The NBOMe drugs, as well as LSD and mescaline, are thought to achieve their psychedelic effects by mimicking the brain chemical serotonin at one of its target sites in the brain (the 5-HT2A receptor). The potency of 25I-NBOMe at this site is comparable to LSD and at least 1000 times higher than mescaline. This means that whereas a typical dose of mescaline would be 200 mg, for both LSD and 25I-NBOMe a few hundred micrograms are usually sufficient. Despite the superficial similarity between LSD and 25I-NBOMe, the two drugs are quite different structurally and their effects are unlikely to be identical.

So, why are the NBOMe drugs such a problem? Here we need to think about how they are taken. Unlike LSD, the NBOMe drugs are not active if they are ingested, so other routes of administration are used. Some have snorted the drugs, some have injected them. This is possible because relatively large amounts of the pure drugs are available. Serious problems can then arise because the drugs are so potent. The effective dose is less than a milligram and this is very difficult for a user to measure accurately. Measurement errors or accidents with the powder can be very dangerous and probably account for the hospitalisations mentioned above.

Another popular route is to transfer small quantities of drug (a milligram or less) on to a small piece of blotting paper; this is usually done by the person selling the drug so that risks to the user are much less. The paper is then placed under the tongue allowing access of the drug to the bloodstream. Many people have taken the drugs this way although users have to trust their supplier to prepare the blotter accurately. The blotters are not expensive and this has tempted some people into taking several at one time. This might well lead to adverse effects because the dose will now be several times higher than the effective dose but this is pure speculation given that we know so little about the short-term physiological effects of these drugs. We also know nothing about the long term effects of these compounds on the brain or their wider toxicology or carcinogenicity so users are taking huge risks.
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The NBOMe story highlights the problems posed by “legal high” drugs. Once a new “legal high” is identified, the response of the authorities in this country is to ban the substance (prohibition). These new drugs are mostly made by labs in the Far East and supplied by dealers or via the internet. The Far Eastern labs know that it takes time to ban each new substance so that when they introduce a new drug to the market, there will be a period of time when they can make money until the drug is banned. Also, banning a drug may reduce its availability but it will usually still be available via the internet. Anyway the banned drug will be replaced quickly by another substance and the cycle will begin again.

In addition, these “legal highs” lack the stringent controls applied to pharmaceuticals. They are often advertised as being of high purity but there is no guarantee that this is true. The compounds are usually poorly characterised in terms of their physiological effects as well as their toxicology and carcinogenicity. Users are taking huge risks in consuming these poorly characterised materials. It is ironic that when 25I-NBOMe was freely available, it was probably safer to take the very well characterised but illegal drug, LSD rather than the “legal high”, NBOMe.

Although banning a drug may give the politicians a nice warm feeling of being in control, this feeling is an illusion.
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For some time I have been convinced that the present system (prohibition) for dealing with “legal highs” and other recreational drugs in the UK is unworkable and is exposing users to unnecessary risks. We have to accept that people want to take drugs and, therefore, we must protect them from harm. One way to achieve this is to move to a system whereby production, supply and use of recreational drugs are regulated. I realise that this would be very unpopular in some parts of society and would be strongly opposed by the present government but I cannot see another way forward.

A good example of a framework for regulation has been put together by The Transform Drug Policy Foundation. Their Blueprint for Regulation contains detailed proposals for regulating production, supply and usage of recreational drugs in this country. Until recently these sorts of proposals were theoretical exercises but in 2011 the New Zealand Government announced its intention to develop a new regime for regulating the manufacture and sale of “low risk” psychoactive substances. This was partly a response to the proliferation of “legal highs” in the country. The market for legal highs in New Zealand does seem to be different from that in the UK. For example, there are surprising reports from New Zealand of the widespread sale of synthetic cannabis-like drugs at local dairies, the New Zealand equivalent of the corner shop or convenience store.

Details of the Psychoactive Substances Bill were released in 2012. In the new framework, manufacturers wishing to sell “low risk” drugs will have to pay for clinical trials of the finished product they wish to market. Approval will be given once the substance has been demonstrated to be of low risk. Sale of the approved substances will also be controlled. The Bill is expected to be approved by the New Zealand Parliament by August 2013. This is a radical new way of dealing with the problems of recreational drug use and many countries will be looking carefully at how New Zealand’s new drug laws work in practice.

[I should like to thank Dr Chris Wilkins of Massey University for help in understanding New Zealand’s “legal high” drug market]

About Philip Strange

After more than 30 years as an experimental scientist, I decided to have a complete change and moved to the West Country. I now write about science for several magazines and web sites and blog at http://philipstrange.wordpress.com/.
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